文献类型：期刊文献

英文题名：Single- and Multiple-Dose Pharmacokinetics of a Novel Tetramethylpyrazine Reservoir-Type Transdermal Patch versus Tetramethylpyrazine Phosphate Oral Tablets in Healthy Normal Volunteers, and in Vitro/in Vivo Correlation

作者：Shen, Teng[1,2];Xu, Huinan[1,2];Weng, Weiyu[3];Zhang, Jianfang[1,2]

机构：[1]Fudan Univ, Sch Pharm, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China;[2]Fudan Univ, Sch Pharm, PLA, Dept Pharmaceut, Shanghai 201203, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2013

卷号：36

期号：6

起止页码：931

外文期刊名：BIOLOGICAL & PHARMACEUTICAL BULLETIN

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000319787400010)】；

基金：This work was supported by National Natural Science Foundation of China (81072594).

语种：英文

外文关键词：tetramethylpyrazine; patch; pharmacokinetics; multiple-dose; transdermal; human skin

摘要：A novel reservoir-type transdermal system of 2,3,5,6-tetramethylpyrazine (TMP) was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. 2,3,5,6-Tetramethylpyrazine phosphate (TMPP) oral tablets were chosen as reference. Following single/multiple oral administration of 200/100mg TMPP tablets, a TMP C-max of 1284/613.5 ng/mL was observed within 0.75h. Single/multiple applications of the TMP patch yielded mean C-max of 309/325 ng/mL at a median T-max of 5/4h, with steady state achieved at second application. The mean C-max of the patch was 131+/-30.38 ng/mL, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250mg/20cm(2) TMP patch given daily provided comparable exposure to 100mg TMPP tablets three times daily (3753.91 versus 3563.67 ng.h/mL). TMP tablets and patch yielded similar steady-state plasma concentrations: C-av (148.48+/-51.27, 156.41+/-40.31 ng/mL). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 mu g/cm(2)/h. The predicted C-av (163.9 ng/mL) was in agreement with the observed C-av (156.4 ng/mL).